Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing

Abstract

Rapid and reliable tailoring of the dose of controlled release tablets to suit an individual patient is a major challenge for personalized medicine. The aim of this work was to investigate the feasibility of using a fused deposition modelling (FDM) based 3D printer to fabricate extended release tablet using prednisolone loaded poly(vinyl alcohol) (PVA) filaments and to control its dose. Prednisolone was loaded into a PVA-based (1.75 mm) filament at approximately 1.9% w/w via incubation in a saturated methanolic solution of prednisolone. The physical form of the drug was assessed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Dose accuracy and in vitro drug release patterns were assessed using HPLC and pH change flow-through dissolution test. Prednisolone loaded PVA filament demonstrated an ability to be fabricated into regular ellipse-shaped solid tablets using the FDM-based 3D printer. It was possible to control the mass of printed tablet through manipulating the volume of the design (R(2) = 0.9983). On printing tablets with target drug contents of 2, 3, 4, 5, 7.5 and 10mg, a good correlation between target and achieved dose was obtained (R(2) = 0.9904) with a dose accuracy range of 88.7-107%. Thermal analysis and XRPD indicated that the majority of prednisolone existed in amorphous form within the tablets. In vitro drug release from 3D printed tablets was extended up to 24h. FDM based 3D printing is a promising method to produce and control the dose of extended release tablets, providing a highly adjustable, affordable, minimally sized, digitally controlled platform for producing patient-tailored medicines.

Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets

“…The demand for versatile and adjustable manufacturing technologies that are capable of overcoming the rigidity and the high cost of traditional manufacturing methods of individualised oral tablets for a limited number of patients is also rising (Yang et al, 2016;Yu et al, 2015). Unlike conventional tablet compression methods, 3D Printing technologies are capable of fabricating small number of dosage forms, reduce the number of steps and experienced operators involved in manufacturing, and eliminate the need for designated and expensive facilities (Skowyra et al, 2015).…”

“…FDM 3D printing is an attractive platform because it offers mechanically stable 1. Introduction 3 printed structures , with high resolution (30-200 µm) (Goyanes et al, 2015a) and a ready-to-use printed objects from the printer platform with no additional postprocessing steps (Goyanes et al, 2015b;Skowyra et al, 2015). Due to the expiration of patents of this technology and the availability of low cost FDM printers, this technology is likely to be widely utilized by a large number of consumers.…”

“…The potential of FDM 3D printing incorporating drugs into commercially available filaments (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) has been explored previously. Nonetheless, all those studies highlighted several challenges involved in employing printing technique for pharmaceutical applications.…”

“…Nonetheless, all those studies highlighted several challenges involved in employing printing technique for pharmaceutical applications. The use of elevated temperatures (185-220 • C) and limited drug loading (0.063-9.5% w/w (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) renders it less suitable for many drugs particularly thermo-labile ones. FDM 3D printing has been also restricted to a number of biodegradable thermoplastic polymers such as polylactic acid (PLA) (Sandler et al, 2014) and polyvinyl alcohol (PVA) (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) in comparison to a wide variety of choices for conventional tabletting.…”

“…FDM 3D printing has been also restricted to a number of biodegradable thermoplastic polymers such as polylactic acid (PLA) (Sandler et al, 2014) and polyvinyl alcohol (PVA) (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015b;Skowyra et al, 2015) in comparison to a wide variety of choices for conventional tabletting. Despite the attractive properties of PVA (Morita et al, 2000) and PLA (Hamad et al, 2016), the use of high polymer ratio in combination with the need for high molecular weight of the polymers generates polymeric matrices with limited porosity, thus resulting in extended drug release patterns (Goyanes et al, 2014a;Goyanes et al, 2014b;Goyanes et al, 2015a;Goyanes et al, 2015b;Sandler et al, 2014;Skowyra et al, 2015).…”